Abstract

BackgroundAs a classic oral drug used in diabetic patients, metformin has exhibited an anticancer role in many types of cancers in recent years. Here, we aimed to investigate the role of metformin in the growth of breast cancer and its novel targets.MethodsA cell viability assay was utilized to examine the inhibitory effect of metformin on proliferation of breast cancer cells. Western blotting and RT‐PCR assays were used to detect the regulation of metformin on the expression of oncogenic HMGA2. The luciferase reporter vector of HMGA2 promoter was constructed. A luciferase reporter gene assay was performed to analyze the effect of metformin on HMGA2 promoter activity in breast cancer cells. Chromatin immunoprecipitation (ChIP) assay was performed to show the binding of Sp1 to HMGA2 promoter in breast cancer cells with or without metformin treatment. The function of metformin‐regulated HMGA2 in breast cancer growth was tested using a cell viability assay.ResultsCell proliferation was obviously inhibited in breast cancer cells treated with different concentrations of metformin. The level of mRNA and protein of HMGA2 was significantly reduced by metformin in the cells. Mechanistically, metformin was able to inactivate the HMGA2 promoter through downregulating transcription factor Sp1 in the cells. In terms of function, treatment with metformin suppressed the proliferation of breast cancer cells and overexpressed HMGA2 reversed the inhibition of cell proliferation mediated by metformin.ConclusionMetformin resists the growth of breast cancer through targeting Sp1/HMGA2 signal.

Highlights

  • Breast cancer is predominantly a malignant tumor in women, with high mortality rates worldwide.[1]

  • Treatment with increased concentrations of metformin significantly reduced the cell viability of breast cancer (Fig 1a,b). These data indicate that metformin is capable of effectively preventing the proliferation of breast cancer cells

  • It has been reported that diabetic patients with metformin treatment had a low incidence of cancer.[3]

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Summary

Introduction

Breast cancer is predominantly a malignant tumor in women, with high mortality rates worldwide.[1]. Metformin together with phenformin play roles in resisting the development of colon cancer through promoting AMPK and ROS production and inhibiting glycolysis.[15–17]. We aimed to investigate the role of metformin in the growth of breast cancer and its novel targets. Methods: A cell viability assay was utilized to examine the inhibitory effect of metformin on proliferation of breast cancer cells. A luciferase reporter gene assay was performed to analyze the effect of metformin on HMGA2 promoter activity in breast cancer cells. Chromatin immunoprecipitation (ChIP) assay was performed to show the binding of Sp1 to HMGA2 promoter in breast cancer cells with or without metformin treatment. The function of metformin-regulated HMGA2 in breast cancer growth was tested using a cell viability assay. Conclusion: Metformin resists the growth of breast cancer through targeting Sp1/HMGA2 signal

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